Developmental and Epileptic Encephalopathies (DEE) are rare neurodevelopmental disorders defined by seizures, developmental delays, and abnormal EEG patterns. Infantile Spasms Syndrome (ISS), the most common DEE, was one of the first linked to single-gene variants, including polyalanine expansions in the Aristaless Related Homeobox (ARX) gene. The Arx^GCG+7 mouse, which models the human mutation, exhibits behavioral phenotypes, epileptiform hippocampal activity, and reduced cholinergic input to the hippocampus. The role of the disrupted cholinergic signaling has not been explored in this model and may be contributing to hippocampal dysfunction and DEE pathogenesis. Hence, we investigated the impact of the ARX GCG expansion on the septo-hippocampal network by first reproducing the changes in Choline acetyltransferase (ChAT) protein levels in the medial septum (MS) and diagonal band of Broca (DBB). Next, we performed ex vivo patch-clamp recordings in CA1 pyramidal neurons and measured responses to cholinergic agonists. Finally, we assessed acetylcholine receptor expression by western blot across the hippocampus to assess for homeostatic changes in receptors. Our data demonstrated a ∼ 60 % reduction in ChAT expression in the MS and DBB of Arx^GCG+7 mice. The Arx^GCG+7 CA1 pyramidal neurons exhibited increased firing activity and reduced sag potential. Despite reduced ChAT, carbachol- and pilocarpine-induced firing responses were preserved, while nicotinic receptor-mediated excitation was abolished. Carbachol-induced depolarization block threshold was elevated in mutants. Molecular analysis revealed increased muscarinic receptor 1 expression and decreased β4 nicotinic receptor expression in CA1.Together, these findings demonstrate histological, electrophysiological, and molecular alterations in the septo-hippocampal network of Arx^GCG+7 mice. Together, they suggest impaired cholinergic signaling contributes to ISS pathogenesis and highlight the cholinergic system as a potential therapeutic target.

2026-01-01·BIOCHEMICAL PHARMACOLOGY

The impact of Vav1 on epileptogenesis and neuronal apoptosis: insights from Sirt1 activation

Article

作者: Zhuo, Zhihong ; Zhao, Haohui ; Wang, Yao ; Kong, Huimin ; Song, Dandan

Epilepsy is a chronic brain disorder characterized by recurrent epileptic seizures, which are caused by abnormal discharges of neurons in the brain. The Vav guanine nucleotide exchange factor (Vav1) has been reported to modulate inflammation and neuronal apoptosis; however, its role in epilepsy remains elusive. This study aimed to investigate the specific function of Vav1 in epileptogenesis and its underlying molecular mechanisms. Rats were challenged with lithium chloride-pilocarpine (LiCl-Pilo) treatment to induce epilepsy model. It was found a high expression of Vav1 in hippocampal tissue of epileptic rats. Vav1 knockdown reduced seizure frequency and mortality in epileptic rats. Besides, LiCl-Pilo treatment-induced spontaneous recurrent seizures was inhibited by Vav1 downregulation, as well as epileptic activity and abnormal sprouting of mossy fibers. We also showed that interfering with the expression of Vav1 alleviates seizure-induced cognitive impairment. Vav1 knockdown restrained neuronal damage and degeneration. Moreover, Sirtuin 1 (Sirt1) was found to regulate the histone acetylation of Vav1 promotor. Sirt1 activation increased the neuronal activity and decreased the neuronal apoptosis, while Vav1 overexpression reversed it. Additionally, the results of mRNA-seq indicated that Vav1 is related to neuronal function and apoptosis regulation. Our study demonstrated that Vav1 accelerates the development of epilepsy, and neuronal damage might be the critical event. These findings could provide a novel direction for epilepsy therapy.

2026-01-01·JOURNAL OF NUTRITIONAL BIOCHEMISTRY

Intermittent fasting preserves the function and histological structure but induces oxidative stress in the salivary glands of male Wistar rats

Article

作者: Barzotti, Renan José ; Dornelles, Rita Cássia Menegati ; Vazão, Arieli Raymundo ; de Lima, José Vitor Furuya ; Sampaio, Larissa Victorino ; Veras, Allice Santos Cruz ; Chaves Neto, Antonio Hernandes ; Nogueira, Fernando Neves ; Teixeira, Giovana Rampazzo ; Nakamune, Ana Claudia de Melo Stevanato

Studies indicate that dietary patterns influence the function and redox balance of salivary glands. This study examined the effects of intermittent fasting (IF) on the function, histological structure, and redox balance of the salivary glands. Twenty 12-week-old male Wistar rats were randomized into two groups: ad libitum (AL), with continuous access to water and chow, and IF, subjected to 24-h fasting on alternate days for 12 weeks. At the end, pilocarpine-induced saliva was collected to analyze flow rate and biochemical composition, while histological structure and redox balance were assessed in the parotid and submandibular glands. IF reduced final body weight and the absolute weight of the submandibular gland while increasing the relative weight of the parotid gland. Salivary flow rate and biochemical parameters, including pH, buffering capacity, amylase, total protein, and electrolyte concentration, were similar between groups. The areas of acini, ducts, and stroma, as well as total oxidant status and markers of lipid and protein oxidative damage, did not differ between groups in either salivary gland. However, IF distinctly affected the antioxidant defense mechanisms of the salivary glands, reducing total antioxidant capacity and increasing catalase (CAT) activity in the parotid glands, while in the submandibular glands, there was higher CAT activity accompanied by reduced superoxide dismutase, glutathione peroxidase, total antioxidant capacity, and reduced glutathione concentrations. Although IF preserved the function and histological structure of the salivary glands in rats, alterations in antioxidant defense indicate oxidative stress.

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项与盐酸毛果芸香碱相关的新闻（医药）

2025-12-23

·汉康资本

汉康Portfolio | 和誉医药CSF-1R抑制剂贝捷迈®获NMPA批准，填补中国腱鞘巨细胞瘤系统性治疗空白

基于全球III期MANEUVER研究的积极数据，中国国家药品监督管理局（NMPA）批准了贝捷迈®（盐酸匹米替尼胶囊）的全球首个新药上市申请，也是中国首个自主研发的腱鞘巨细胞瘤（TGCT）系统性治疗药物。默克作为我们的合作伙伴，拥有贝捷迈®在全球的商业化权益。贝捷迈®是和誉医药自主研发的1类新药，上市申请（NDA）获受理后仅6个多月即实现零发补批准。期间顺利通过国家药监局核查中心（CFDI）首次赴海外临床中心开展的现场核查，不仅体现了和誉医药研发体系的严格标准，也彰显了监管机构对贝捷迈®临床价值和数据质量的高度认可。贝捷迈®获批用于治疗TGCT，这标志着公司从开创性的创新研究迈向首个产品商业化的关键里程碑。 2025年12月22日，上海和誉生物医药科技有限公司（以下简称“和誉医药”，港交所代码：02256）宣布，其自主研发的CSF-1R高选择性小分子抑制剂贝捷迈®（盐酸匹米替尼胶囊）获得中国国家药品监督管理局（NMPA）批准，适用于手术切除可能会导致功能受限或出现较严重并发症的症状性腱鞘巨细胞瘤（TGCT）成年患者。获批后，默克将尽快推动该产品惠及中国TGCT患者。汉康资本于2017年领投和誉医药A+轮融资，并在后续轮次继续支持。腱鞘巨细胞瘤是一种罕见的局部侵袭性肿瘤，主要累及关节、腱鞘及滑囊，可导致严重的局部病变和功能障碍。其发生机制为肿瘤性滑膜细胞中过度表达集落刺激因子1（CSF-1），从而导致表达集落刺激因子1受体（CSF-1R）的炎症细胞在肿瘤中大量聚集。《中国腱鞘巨细胞瘤临床诊疗专家共识》明确指出，对于不可切除的TGCT，推荐采用CSF-1/CSF-1R通路抑制剂进行治疗（推荐等级：1级；证据等级：A级）。 “长期以来，中国有许多TGCT患者缺乏手术之外的治疗选择，而手术可能无法满足肿瘤复发或无法切除的患者的治疗需求。”北京积水潭医院骨与软组织肿瘤诊疗中心主任牛晓辉教授表示，“此次基于MANEUVER研究结果获批的贝捷迈®，为中国临床医生提供了一种有效且耐受性良好的系统性治疗方案，有望显著改变该疾病的临床治疗格局。” 贝捷迈®是一款由和誉医药独立研发的新型、可口服、高选择性且高效的小分子CSF-1R抑制剂，本次获NMPA批准基于全球III期MANEUVER研究的积极结果。研究显示，贝捷迈®在所有TGCT系统性治疗III期研究中，实现了迄今基于RECIST v1.1标准评估的最高客观缓解率（ORR）。第25周时，经盲态独立评审委员会（BIRC）基于RECIST v1.1标准评估，贝捷迈®在主要终点ORR上显著优于安慰剂对照组（54.0% vs. 3.2%，P＜0.0001）。在多项与患者生活质量密切相关的关键次要终点上，贝捷迈®均取得了具有临床意义的显著改善，包括提升关节活动度（p=0.0003）、改善躯体功能（PROMIS-PF；p=0.0074），以及减轻最严重僵硬感（p<0.0001）和最严重疼痛（p<0.0001）。2025年欧洲肿瘤内科学会（ESMO）大会上公布的长期随访数据进一步表明，贝捷迈®可以为TGCT患者带来强劲而持久的肿瘤缓解疗效。中位随访14.3个月时，自研究开始即接受贝捷迈®治疗的患者，ORR从第25周的54%显著提升至76.2%（95% CI：63.8，86.0），其中4例实现完全缓解。和誉医药创始人兼首席执行官徐耀昌博士表示：“此次获批不仅是一个监管里程碑，更是和誉医药发展历程中具有决定性意义的时刻。它标志着我们从科学创新的开拓者，成长为能为患者带来突破性疗法的企业。秉持着解决真实临床需求的坚定信念，我们将继续推进具有突破性和差异化优势的药物研发，以期重塑中国乃至全球肿瘤及其他疾病领域的治疗格局。贝捷迈®作为中国首个自主研发获批的CSF-1R抑制剂，不仅填补了腱鞘巨细胞瘤（TGCT）治疗的关键空白，更印证了我们以全球视野践行创新理念，将前沿构想转化为临床价值的决心与能力。” 默克医药健康首席执行官、默克执行董事会成员丹卓航表示: “随着贝捷迈®在全球的首个注册获批，我们正持续践行改善罕见肿瘤患者生活的承诺。此次获批更是进一步夯实我们在罕见肿瘤领导地位的关键一步。我们为患者带来了既能改变疾病进程、又可缓解日常症状的希望。我们正在加速推进贝捷迈®早日惠及中国患者，并持续推进其在全球其他市场的注册布局。” 在MANEUVER研究中，贝捷迈®还展现出良好的安全性和耐受性。治疗期间，患者的中位剂量强度保持在88.2%的较高水平。大多数治疗相关不良事件（TEAEs）为1-2级，未观察到新的安全性信号，亦无胆汁淤积性肝毒性、药物性肝损伤或毛发/皮肤色素减退等相关证据。关于贝捷迈®（盐酸匹米替尼胶囊）贝捷迈®是由和誉医药独立研发的一款新型、口服、高选择性且高效的小分子CSF-1R抑制剂，其在全球III期MANEUVER研究中针对腱鞘巨细胞瘤（TGCT）的积极顶线结果已于2024年11月成功发布。目前，贝捷迈®已获中国国家药品监督管理局（NMPA）批准，适用于手术切除可能会导致功能受限或出现较严重并发症的症状性腱鞘巨细胞瘤（TGCT）成年患者。2023年12月，和誉医药与默克公司就贝捷迈®的商业化权利达成协议，默克公司会负责贝捷迈®在全球的商业化。 Abbisko Therapeutics' CSF-1R Inhibitor Pimicotinib Approved by the China NMPA, Addressing the Treatment Gap for Tenosynovial Giant Cell Tumor Based on the positive global Phase III MANEUVER study, the National Medical Products Administration (NMPA) has granted the world's first regulatory approval for pimicotinib, the first domestically developed systemic therapy for the treatment of Tenosynovial Giant Cell Tumor (TGCT), to our partner Merck KGaA, Darmstadt, Germany, which holds worldwide commercialization rights. Pimicotinib, a Class 1 innovative drug discovered and developed by Abbisko Therapeutics, received zero-deficiency approval in just over six months following NDA acceptance. During the review, the Center for Food and Drug Inspection (CFDI) conducted its first-ever overseas clinical site inspection for pimicotinib, which it successfully passed. This outcome reflects Abbisko's rigorous R&D standards and regulators' strong recognition of the therapy's clinical value and data quality. Pimicotinib's approval for the treatment of TGCT marks a key milestone in the company's advancement from pioneering innovative research to first product commercialization. 22 November 2025, Shanghai – Abbisko Therapeutics Co., Ltd. ("Abbisko Therapeutics" hereafter, HKEX code: 02256.HK) today announced that the China National Medical Products Administration (NMPA) has approved pimicotinib for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause functional limitation or severe morbidity. Following this approval, Merck KGaA, Darmstadt, Germany, is working to ensure timely patient access in China. TGCT is a rare and locally aggressive tumor primarily affecting joints, tendon sheaths, and bursae with considerable morbidity and functional impairment. TGCT is driven by overexpression of colony-stimulating factor-1 (CSF-1) in neoplastic synovial cells which leads to accumulation of colony-stimulating factor-1 receptor (CSF-1R)–expressing inflammatory cells in the tumor. The Chinese expert consensus on clinical diagnosis and treatment of TGCT recommends CSF-1/CSF-1R pathway inhibitors as the preferred systemic treatment for patients with unresectable TGCT (Recommendation Level I; Evidence Level A). "Many people living with TGCT in China have faced a long and difficult journey due to the lack of approved options beyond surgery, which may not address the needs of patients whose tumors recur or are not amenable to resection," said Prof. Niu Xiaohui, Director of the Bone and Soft Tissue Tumour Diagnosis and Research Centre at Beijing Jishuitan Hospital. "With the approval of pimicotinib based on the results of the global MANEUVER study, healthcare professionals in China will soon have the opportunity to prescribe their patients an effective and well-tolerated systemic treatment option, offering a much-needed advance in how they manage this challenging condition." Pimicotinib is a novel, oral, highly selective, and potent small-molecule CSF-1R inhibitor independently developed by Abbisko Therapeutics. The approval by the China NMPA is based on the positive results from the global Phase III MANEUVER study, in which pimicotinib demonstrated the highest objective response rate (ORR) based on RECIST v1.1 seen in a Phase III clinical trial for the treatment TGCT. At week 25, pimicotinib demonstrated a statistically significant improvement in the primary endpoint of ORR compared with placebo (54.0% vs. 3.2%, respectively; p<0.0001) as assessed by Blinded Independent Review Committee (BIRC) based on RECIST v1.1. pimicotinib also demonstrated clinically meaningful and statistically significant improvements across secondary endpoints relevant to patient daily life, improving relative Range of Motion (p=0.0003) and physical function as measured by the PROMIS-PF scale (p=0.0074), as well as reducing Worst Stiffness NRS (p<0.0001) and BPI Worst Pain NRS (p<0.0001). Longer-term follow-up data presented at the 2025 European Society for Medical Oncology (ESMO) Congress further demonstrated that pimicotinib provides robust and durable tumor responses for patients with TGCT. With a median follow-up of 14.3 months, ORR per RECIST v1.1 increased from 54% at week 25 to 76.2% (95% CI: 63.8, 86.0), including four patients achieving a Complete Response (CR). Dr. Yaochang Xu, Founder and Chief Executive Officer of Abbisko Therapeutics, stated: "The approval of pimicotinib is far more than a regulatory milestone—it is a defining moment in Abbisko's journey. It reflects our evolution from pioneers in scientific innovation to a company capable of bringing meaningful therapies to patients. Guided by an unwavering commitment to addressing real clinical needs, we will continue advancing breakthrough, differentiated medicines that have the potential to reshape the future of oncology and other disease areas in China and around the world. As the first domestically independently developed CSF-1R inhibitor approved in China, pimicotinib not only fills a crucial gap for patients with TGCT, but also exemplifies what we can achieve when we pursue bold ideas with global ambition and a relentless focus on impact." "We are continuing to deliver on our commitment to improving the lives of patients with rare tumors with this first-in-the-world regulatory approval of pimicotinib," said Danny Bar-Zohar, CEO Healthcare and Member of the Executive Board of Merck KGaA, Darmstadt, Germany. "This approval is a significant step forward in further strengthening our leadership in rare tumors, while offering patients the opportunity to change the course of their disease and help alleviate symptoms that impact their daily lives. We are now working to make pimicotinib available to patients in China as quickly as possible, as we continue to progress applications with regulatory authorities in additional markets." In the MANEUVER study, pimicotinib also demonstrated a generally well-tolerated safety profile. The median dose intensity remained high at 88.2% during treatment. Most treatment-emergent adverse events (TEAEs) were Grade 1-2. No new safety signals were observed with longer-term follow-up, and there was no evidence of cholestatic hepatotoxicity, drug-induced liver injury, or hair/skin hypopigmentation. About Pimicotinib Pimicotinib is a novel, oral, highly selective, and potent small-molecule CSF-1R inhibitor independently developed by Abbisko Therapeutics. Positive results from the global Phase III MANEUVER study of pimicotinib for the treatment of Tenosynovial Giant Cell Tumor (TGCT) were announced in November 2024. Currently, pimicotinib has been approved by the National Medical Products Administration (NMPA) in China for the treatment of adult patients with symptomatic TGCT for which surgical resection may potentially cause functional limitation or relatively severe morbidity. In December 2023, Abbisko entered into an agreement with Merck KGaA, Darmstadt, Germany, pertaining to the commercial rights to pimicotinib, pursuant to which Merck KGaA, Darmstadt, Germany, is responsible for the commercialization of pimicotinib globally. Outside of China, pimicotinib has been granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) and PRIME Designation by the European Medicines Agency (EMA). About Abbisko Therapeutics Founded in April 2016, Abbisko Therapeutics Co., Ltd. (HKEX: 02256.HK), is an oncology-focused biopharmaceutical company based in Shanghai that is dedicated to the discovery and development of innovative medicines to treat unmet medical needs in China and globally. The Company was established by a group of seasoned drug hunters with rich research & development and managerial expertise from top multinational pharmaceutical companies. Since its founding, Abbisko Therapeutics has built an extensive pipeline of innovative programs focused on precision oncology and immuno-oncology. 关于和誉医药和誉医药（香港联交所代码：02256）成立于2016年，是一家立足中国，着眼全球的创新药研发公司。公司的创始人和管理团队拥有多年顶尖跨国药企的研发和管理经验，并参与了多个临床及上市新药的研发。和誉医药专注于肿瘤新药研发，以小分子肿瘤精准治疗和小分子肿瘤免疫治疗药物为核心，着眼病患及医药市场的需求，秉承国际新药开发的理念和标准，致力于开发新颖及高潜力药物靶点的潜在first-in-class或best-in-class创新药物，用于改善中国及全球病人的生活质量。自成立以来，和誉医药已经建立了丰富的创新产品管线，涵盖肿瘤精准治疗领域以及肿瘤免疫治疗领域。关于汉康资本汉康资本是一家专注于医药健康产业的风险投资基金。基金以“赋能医药创新，守护人类健康”为使命，携手一流科学家和企业家共同开发治疗重大疾病的突破性新药。汉康资本立足中国，放眼世界，投资的多家企业已成长为行业领先企业，如康方生物（09926.HK）、诺诚健华（09969.HK，688428.SH）、康诺亚生物（02162.HK）、和誉医药（02256.HK）、映恩生物（09606.HK）、维立志博（09887.HK）、微芯生物（688321.SH）、奥浦迈（688293.SH）等。

临床3期申请上市临床结果临床成功

2025-12-22

·上海和誉生物医药科技有限公司

和誉医药CSF-1R抑制剂贝捷迈®获NMPA批准，填补中国腱鞘巨细胞瘤系统性治疗空白

基于全球III期MANEUVER研究的积极数据，中国国家药品监督管理局（NMPA）批准了贝捷迈®（盐酸匹米替尼胶囊）的全球首个新药上市申请，也是中国首个自主研发的腱鞘巨细胞瘤（TGCT）系统性治疗药物。默克作为我们的合作伙伴，拥有贝捷迈®在全球的商业化权益。贝捷迈®是和誉医药自主研发的1类新药，上市申请（NDA）获受理后仅6个多月即实现零发补批准。期间顺利通过国家药品审评检查中心（CFDI）首次赴海外临床中心开展的现场核查，不仅体现了和誉医药研发体系的严格标准，也彰显了监管机构对贝捷迈®临床价值和数据质量的高度认可。贝捷迈®获批用于治疗TGCT，这标志着公司从开创性的创新研究迈向首个产品商业化的关键里程碑。 2025年12月22日，上海和誉生物医药科技有限公司（以下简称“和誉医药”，港交所代码：02256）今日宣布，其自主研发的CSF-1R高选择性小分子抑制剂贝捷迈®（盐酸匹米替尼胶囊）获得中国国家药品监督管理局（NMPA）批准，适用于手术切除可能会导致功能受限或出现较严重并发症的症状性腱鞘巨细胞瘤（TGCT）成年患者。获批后，默克将尽快推动该产品惠及中国TGCT患者。腱鞘巨细胞瘤是一种罕见的局部侵袭性肿瘤，主要累及关节、腱鞘及滑囊，可导致严重的局部病变和功能障碍。其发生机制为肿瘤性滑膜细胞中过度表达集落刺激因子1（CSF-1），从而导致表达集落刺激因子1受体（CSF-1R）的炎症细胞在肿瘤中大量聚集。《中国腱鞘巨细胞瘤临床诊疗专家共识》明确指出，对于不可切除的TGCT，推荐采用CSF-1/CSF-1R通路抑制剂进行治疗（推荐等级：1级；证据等级：A级）。 “长期以来，中国有许多TGCT患者缺乏手术之外的治疗选择，而手术可能无法满足肿瘤复发或无法切除的患者的治疗需求。”北京积水潭医院骨与软组织肿瘤诊疗中心主任牛晓辉教授表示，“此次基于MANEUVER研究结果获批的贝捷迈®，为中国临床医生提供了一种有效且耐受性良好的系统性治疗方案，有望显著改变该疾病的临床治疗格局。” 贝捷迈®是一款由和誉医药独立研发的新型、可口服、高选择性且高效的小分子CSF-1R抑制剂，本次获NMPA批准基于全球III期MANEUVER研究的积极结果。研究显示，贝捷迈®在所有TGCT系统性治疗III期研究中，实现了迄今基于RECIST v1.1标准评估的最高客观缓解率（ORR）。第25周时，经盲态独立评审委员会（BIRC）基于RECIST v1.1标准评估，贝捷迈®在主要终点ORR上显著优于安慰剂对照组（54.0% vs. 3.2%，P＜0.0001）。在多项与患者生活质量密切相关的关键次要终点上，贝捷迈®均取得了具有临床意义的显著改善，包括提升关节活动度（p=0.0003）、改善躯体功能（PROMIS-PF；p=0.0074），以及减轻最严重僵硬感（p<0.0001）和最严重疼痛（p<0.0001）。2025年欧洲肿瘤内科学会（ESMO）大会上公布的长期随访数据进一步表明，贝捷迈®可以为TGCT患者带来强劲而持久的肿瘤缓解疗效。中位随访14.3个月时，自研究开始即接受贝捷迈®治疗的患者，ORR从第25周的54%显著提升至76.2%（95% CI：63.8，86.0），其中4例实现完全缓解。和誉医药创始人兼首席执行官徐耀昌博士表示：“此次获批不仅是一个监管里程碑，更是和誉医药发展历程中具有决定性意义的时刻。它标志着我们从科学创新的开拓者，成长为能为患者带来突破性疗法的企业。秉持着解决真实临床需求的坚定信念，我们将继续推进具有突破性和差异化优势的药物研发，以期重塑中国乃至全球肿瘤及其他疾病领域的治疗格局。贝捷迈®作为中国首个自主研发获批的CSF-1R抑制剂，不仅填补了腱鞘巨细胞瘤（TGCT）治疗的关键空白，更印证了我们以全球视野践行创新理念，将前沿构想转化为临床价值的决心与能力。” 默克医药健康首席执行官、默克执行董事会成员丹卓航表示: “随着贝捷迈®在全球的首个注册获批，我们正持续践行改善罕见肿瘤患者生活的承诺。此次获批更是进一步夯实我们在罕见肿瘤领导地位的关键一步。我们为患者带来了既能改变疾病进程、又可缓解日常症状的希望。我们正在加速推进贝捷迈®早日惠及中国患者，并持续推进其在全球其他市场的注册布局。” 在MANEUVER研究中，贝捷迈®还展现出良好的安全性和耐受性。治疗期间，患者的中位剂量强度保持在88.2%的较高水平。大多数治疗相关不良事件（TEAEs）为1-2级，未观察到新的安全性信号，亦无胆汁淤积性肝毒性、药物性肝损伤或毛发/皮肤色素减退等相关证据。关于贝捷迈®（盐酸匹米替尼胶囊）贝捷迈®是由和誉医药独立研发的一款新型、口服、高选择性且高效的小分子CSF-1R抑制剂，其在全球III期MANEUVER研究中针对腱鞘巨细胞瘤（TGCT）的积极顶线结果已于2024年11月成功发布。目前，贝捷迈®已获中国国家药品监督管理局（NMPA）批准，适用于手术切除可能会导致功能受限或出现较严重并发症的症状性腱鞘巨细胞瘤（TGCT）成年患者。2023年12月，和誉医药与默克公司就贝捷迈®的商业化权利达成协议，默克公司会负责贝捷迈®在全球的商业化。 Abbisko Therapeutics' CSF-1R Inhibitor Pimicotinib Approved by the China NMPA, Addressing the Treatment Gap for Tenosynovial Giant Cell Tumor Based on the positive global Phase III MANEUVER study, the National Medical Products Administration (NMPA) has granted the world's first regulatory approval for pimicotinib, the first domestically developed systemic therapy for the treatment of Tenosynovial Giant Cell Tumor (TGCT), to our partner Merck KGaA, Darmstadt, Germany, which holds worldwide commercialization rights. Pimicotinib, a Class 1 innovative drug discovered and developed by Abbisko Therapeutics, received zero-deficiency approval in just over six months following NDA acceptance. During the review, the Center for Food and Drug Inspection (CFDI) conducted its first-ever overseas clinical site inspection for pimicotinib, which it successfully passed. This outcome reflects Abbisko's rigorous R&D standards and regulators' strong recognition of the therapy's clinical value and data quality. Pimicotinib's approval for the treatment of TGCT marks a key milestone in the company's advancement from pioneering innovative research to first product commercialization. 22 November 2025, Shanghai – Abbisko Therapeutics Co., Ltd. ("Abbisko Therapeutics" hereafter, HKEX code: 02256.HK) today announced that the China National Medical Products Administration (NMPA) has approved pimicotinib for the treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause functional limitation or severe morbidity. Following this approval, Merck KGaA, Darmstadt, Germany, is working to ensure timely patient access in China. TGCT is a rare and locally aggressive tumor primarily affecting joints, tendon sheaths, and bursae with considerable morbidity and functional impairment. TGCT is driven by overexpression of colony-stimulating factor-1 (CSF-1) in neoplastic synovial cells which leads to accumulation of colony-stimulating factor-1 receptor (CSF-1R)–expressing inflammatory cells in the tumor. The Chinese expert consensus on clinical diagnosis and treatment of TGCT recommends CSF-1/CSF-1R pathway inhibitors as the preferred systemic treatment for patients with unresectable TGCT (Recommendation Level I; Evidence Level A). "Many people living with TGCT in China have faced a long and difficult journey due to the lack of approved options beyond surgery, which may not address the needs of patients whose tumors recur or are not amenable to resection," said Prof. Niu Xiaohui, Director of the Bone and Soft Tissue Tumour Diagnosis and Research Centre at Beijing Jishuitan Hospital. "With the approval of pimicotinib based on the results of the global MANEUVER study, healthcare professionals in China will soon have the opportunity to prescribe their patients an effective and well-tolerated systemic treatment option, offering a much-needed advance in how they manage this challenging condition." Pimicotinib is a novel, oral, highly selective, and potent small-molecule CSF-1R inhibitor independently developed by Abbisko Therapeutics. The approval by the China NMPA is based on the positive results from the global Phase III MANEUVER study, in which pimicotinib demonstrated the highest objective response rate (ORR) based on RECIST v1.1 seen in a Phase III clinical trial for the treatment TGCT. At week 25, pimicotinib demonstrated a statistically significant improvement in the primary endpoint of ORR compared with placebo (54.0% vs. 3.2%, respectively; p<0.0001) as assessed by Blinded Independent Review Committee (BIRC) based on RECIST v1.1. pimicotinib also demonstrated clinically meaningful and statistically significant improvements across secondary endpoints relevant to patient daily life, improving relative Range of Motion (p=0.0003) and physical function as measured by the PROMIS-PF scale (p=0.0074), as well as reducing Worst Stiffness NRS (p<0.0001) and BPI Worst Pain NRS (p<0.0001). Longer-term follow-up data presented at the 2025 European Society for Medical Oncology (ESMO) Congress further demonstrated that pimicotinib provides robust and durable tumor responses for patients with TGCT. With a median follow-up of 14.3 months, ORR per RECIST v1.1 increased from 54% at week 25 to 76.2% (95% CI: 63.8, 86.0), including four patients achieving a Complete Response (CR). Dr. Yaochang Xu, Founder and Chief Executive Officer of Abbisko Therapeutics, stated: "The approval of pimicotinib is far more than a regulatory milestone—it is a defining moment in Abbisko's journey. It reflects our evolution from pioneers in scientific innovation to a company capable of bringing meaningful therapies to patients. Guided by an unwavering commitment to addressing real clinical needs, we will continue advancing breakthrough, differentiated medicines that have the potential to reshape the future of oncology and other disease areas in China and around the world. As the first domestically independently developed CSF-1R inhibitor approved in China, pimicotinib not only fills a crucial gap for patients with TGCT, but also exemplifies what we can achieve when we pursue bold ideas with global ambition and a relentless focus on impact." "We are continuing to deliver on our commitment to improving the lives of patients with rare tumors with this first-in-the-world regulatory approval of pimicotinib," said Danny Bar-Zohar, CEO Healthcare and Member of the Executive Board of Merck KGaA, Darmstadt, Germany. "This approval is a significant step forward in further strengthening our leadership in rare tumors, while offering patients the opportunity to change the course of their disease and help alleviate symptoms that impact their daily lives. We are now working to make pimicotinib available to patients in China as quickly as possible, as we continue to progress applications with regulatory authorities in additional markets." In the MANEUVER study, pimicotinib also demonstrated a generally well-tolerated safety profile. The median dose intensity remained high at 88.2% during treatment. Most treatment-emergent adverse events (TEAEs) were Grade 1-2. No new safety signals were observed with longer-term follow-up, and there was no evidence of cholestatic hepatotoxicity, drug-induced liver injury, or hair/skin hypopigmentation. About Pimicotinib Pimicotinib is a novel, oral, highly selective, and potent small-molecule CSF-1R inhibitor independently developed by Abbisko Therapeutics. Positive results from the global Phase III MANEUVER study of pimicotinib for the treatment of Tenosynovial Giant Cell Tumor (TGCT) were announced in November 2024. Currently, pimicotinib has been approved by the National Medical Products Administration (NMPA) in China for the treatment of adult patients with symptomatic TGCT for which surgical resection may potentially cause functional limitation or relatively severe morbidity. In December 2023, Abbisko entered into an agreement with Merck KGaA, Darmstadt, Germany, pertaining to the commercial rights to pimicotinib, pursuant to which Merck KGaA, Darmstadt, Germany, is responsible for the commercialization of pimicotinib globally. Outside of China, pimicotinib has been granted Breakthrough Therapy Designation by the US Food and Drug Administration (FDA) and PRIME Designation by the European Medicines Agency (EMA). About Abbisko Therapeutics Founded in April 2016, Abbisko Therapeutics Co., Ltd. (HKEX: 02256.HK), is an oncology-focused biopharmaceutical company based in Shanghai that is dedicated to the discovery and development of innovative medicines to treat unmet medical needs in China and globally. The Company was established by a group of seasoned drug hunters with rich research & development and managerial expertise from top multinational pharmaceutical companies. Since its founding, Abbisko Therapeutics has built an extensive pipeline of innovative programs focused on precision oncology and immuno-oncology. Please visit www.abbisko.com for more information. 关于和誉和誉医药（香港联交所代码：02256）成立于2016年，是一家立足中国，着眼全球的创新药研发公司。公司的创始人和管理团队拥有多年顶尖跨国药企的研发和管理经验，并参与了多个临床及上市新药的研发。和誉医药专注于肿瘤新药研发，以小分子肿瘤精准治疗和小分子肿瘤免疫治疗药物为核心，着眼病患及医药市场的需求，秉承国际新药开发的理念和标准，致力于开发新颖及高潜力药物靶点的潜在first-in-class或best-in-class创新药物，用于改善中国及全球病人的生活质量。自成立以来，和誉医药已经建立了丰富的创新产品管线，涵盖肿瘤精准治疗领域以及肿瘤免疫治疗领域。更多信息，欢迎访问 www.abbisko.com。

临床3期申请上市优先审批临床申请临床结果

2025-12-15

·EndPoints

Lenz discloses case of retinal tear in presbyopia eye drop patient

Lenz Therapeutics alarmed investors on Friday when it disclosed a report of a serious complication in a patient who took its commercial eye drop for blurry near vision. The drug, called Vizz, was approved in July to treat presbyopia. Since then, a case of retinal tear was reported to the FDA’s adverse event database known as FAERS. The system collects self-submitted reports from healthcare workers, patients and others, and “does not equate to a causal relationship,” Lenz wrote in a securities filing. The company’s stock $LENZ fell 26% following the announcement on Friday. Then on Monday afternoon, the stock was down 7%, pricing at about $17 per share. Rips in the retina, the light-sensitive tissue in the back of the eye, can cause vision problems such as floaters. TD Cowen analysts wrote in a note to investors on Friday that they expected “very understandable investor worry” in response to the FAERS report. But they noted that based on current information, the incident represents one case following at least 5,000 Vizz prescriptions, which doesn’t count many other patients who have likely received Vizz as well “given the substantial sampling.” Lenz told Endpoints News in an emailed statement on Monday that retinal tears occur naturally in roughly 25 per 100,000 people every year. “As real-world use of Vizz expands, occasional retinal events may be expected, and this initial case occurring in a patient with significant baseline risk, including past retinal tears, does not change our overall safety expectations for Vizz nor who should be prescribed it,” the company said. The patient is “recovering well,” according to Lenz’s securities filing. Vizz’s label carries a warning for rare cases of retinal tears, but Lenz told Endpoints that no patients experienced retinal tears in clinical trials for the drug. The TD Cowen analysts noted that a perceived risk of retinal detachment impacted the launch of AbbVie’s competitor product Vuity, beyond other efficacy problems for the drug. Vuity’s label notes that “rare cases of retinal detachment and retinal tear have been reported with miotics, including Vuity.” AbbVie won the first approval for a presbyopia eye drop in 2021, but reduced its marketing and sales efforts on the drug shortly thereafter. Lenz has claimed that Vizz is more effective than Vuity, and works longer. However, the company has not conducted a head-to-head trial comparing the products directly.

上市批准

100 项与盐酸毛果芸香碱相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D02200	盐酸毛果芸香碱	S01EB01 N07AX01	DB01085

研发状态

批准上市

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适应症	国家/地区	公司	日期
老花眼	美国	AbbVie, Inc.	2021-10-28
急性闭角型青光眼	美国	Sandoz, Inc.	2010-06-22
高眼压症	美国	ALCON INC	1984-10-01
口干症	加拿大	Alcon Canada, Inc.	1951-12-31

未上市

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适应症	最高研发状态	国家/地区	公司	日期
干燥综合征性角膜结膜炎	临床2期	美国	Glaukos Corp.	2022-01-03
干眼症	临床2期	美国	Glaukos Corp.	-
瞳孔缩小	临床1期	美国	Novus Vision LLC	2025-01-30

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05393895 (CTgov)	临床3期	老花眼	178	CSF-1 (CSF-1)	製壓廠築膚衊鹹願淵觸 = 鹽積艱鬱衊遞簾淵觸餘壓醖艱窪糧構構繭衊壓 (築窪壓襯夢構遞醖繭鬱, 構製鏇襯製鹽壓鑰壓獵 ~ 鏇醖網餘淵鹹鹽築製窪) 更多	-	2025-06-11
				Vehicle (Vehicle)	製壓廠築膚衊鹹願淵觸 = 糧鏇醖壓鏇簾憲糧襯製壓醖艱窪糧構構繭衊壓 (築窪壓襯夢構遞醖繭鬱, 鬱艱鹽襯鹽顧鏇壓構餘 ~ 蓋願鹽壓鹽築觸壓壓餘) 更多
NCT04599933 (NEAR-1, CTgov)	临床3期	老花眼	309	CSF-1 (CSF-1)	構願鬱醖積構壓願窪膚 = 觸壓窪齋築鏇築壓獵窪構積遞糧範淵憲簾夢淵 (構願鹽齋糧製選鑰窪遞, 積壓糧願餘淵齋觸艱範 ~ 顧襯廠鹹蓋鏇觸窪衊壓) 更多	-	2023-11-28
				Vehicle (Vehicle)	構願鬱醖積構壓願窪膚 = 鹹網範選膚鑰壓顧壓窪構積遞糧範淵憲簾夢淵 (構願鹽齋糧製選鑰窪遞, 繭觸鹽艱選齋顧膚窪選 ~ 願衊鹹簾積襯鏇餘範憲) 更多
NCT04599972 (NEAR-2, CTgov)	临床3期	老花眼	304	CSF-1 (CSF-1)	壓鑰製衊襯顧鹹廠範鏇 = 艱膚餘衊積繭鹽構衊遞鏇憲繭網觸簾積壓簾遞 (鬱選鹹製壓壓衊衊簾窪, 廠壓簾網鏇願鹽築鹹糧 ~ 襯鹽遞衊襯艱醖艱鏇鏇) 更多	-	2023-11-28
				Vehicle (Vehicle)	壓鑰製衊襯顧鹹廠範鏇 = 築鏇選築窪範鏇顧獵顧鏇憲繭網觸簾積壓簾遞 (鬱選鹹製壓壓衊衊簾窪, 窪膚壓夢鬱製憲齋襯憲 ~ 齋顧遞鏇範鏇鹽選顧夢) 更多
NCT04675151 (CTgov)	临床2期	老花眼	150	LDP+POS (POS 0.75% First, Then LDP 0.4%)	觸獵廠膚廠鹽願壓衊壓 = 鹽艱顧廠選衊蓋簾簾衊獵齋醖願網淵淵鹹艱鹽 (願獵遞獵壓蓋壓鹽糧餘, 膚鹹顧齋糧鏇範獵齋齋 ~ 廠餘願遞構衊遞構鹽製) 更多	-	2023-08-02
				LDP+POS (POS 0.75% First, Then LDP Vehicle)	觸獵廠膚廠鹽願壓衊壓 = 繭醖襯襯顧醖蓋艱艱築獵齋醖願網淵淵鹹艱鹽 (願獵遞獵壓蓋壓鹽糧餘, 鬱鹹顧觸壓膚襯鹽鹽製 ~ 積製鏇鹹範糧鹹淵鏇鬱) 更多
GEMINI (ARVO2023)	临床3期	老花眼	750	Pilocarpine HCl ophthalmic solution 1.25%	鹽簾遞衊憲遞壓選觸壓(廠壓遞網築壓簾廠憲淵) = 艱網網構憲憲鹹鹹蓋淵積醖顧餘糧窪鬱積衊獵 (觸網觸繭鏇觸襯鹽築鬱 ) 更多	-	2023-06-01
				Vehicle	鹽簾遞衊憲遞壓選觸壓(廠壓遞網築壓簾廠憲淵) = 衊齋糧願衊鑰網願顧鹹積醖顧餘糧窪鬱積衊獵 (觸網觸繭鏇觸襯鹽築鬱 ) 更多
ARVO2023	临床2期	老花眼	150	0.75% Phentolamine Ophthalmic Solution (POS)	範繭遞繭淵鹽遞齋廠襯(鹽衊鬱網築繭範築餘窪) = 鹽築遞窪積夢蓋繭範鹹鏇蓋蓋遞鬱夢衊顧積憲 (壓壓遞製遞壓網夢鏇膚 )	积极	2023-04-23
				0.4% Low Dose Pilocarpine (LDP)	範繭遞繭淵鹽遞齋廠襯(鹽衊鬱網築繭範築餘窪) = 鹹鏇鏇衊遞繭窪鹽艱膚鏇蓋蓋遞鬱夢衊顧積憲 (壓壓遞製遞壓網夢鏇膚 )
NCT03804268 (GEMINI 1, ARVO2023)	临床3期	老花眼	323	Pilocarpine hydrochloride ophthalmic solution 1.25%	願選齋鹽醖醖鏇窪鬱願(網選鹽襯淵蓋簾積願襯) = 廠製繭構網範齋鹹鏇鏇廠築選鹹鏇範憲繭築襯 (糧繭艱餘遞壓範艱膚齋 )	-	2023-04-23
				Vehicle	願選齋鹽醖醖鏇窪鬱願(網選鹽襯淵蓋簾積願襯) = 選夢餘襯繭醖壓糧衊壓廠築選鹹鏇範憲繭築襯 (糧繭艱餘遞壓範艱膚齋 )
NCT04983589 (Virgo, CTgov)	临床3期	老花眼	230	Vehicle (Vehicle)	繭淵壓襯齋顧艱鏇蓋獵 = 鹽顧糧憲壓糧餘淵繭齋範鑰蓋艱築餘齋廠網糧 (鑰鑰積鑰選鏇艱繭艱選, 膚積齋窪積淵鑰築遞鹽 ~ 鑰糧餘齋夢積構蓋襯獵) 更多	-	2023-03-21
				Pilocarpine HCl (AGN-190584)	繭淵壓襯齋顧艱鏇蓋獵 = 鬱糧顧繭鑰齋顧夢鹹範範鑰蓋艱築餘齋廠網糧 (鑰鑰積鑰選鏇艱繭艱選, 廠窪鏇繭製繭齋鏇糧鑰 ~ 膚鬱廠膚淵範壓遞襯鬱) 更多
NCT05238233 (CTgov)	临床4期	瞳孔不等	11	Reichert phoropter+Proparacaine Hydrochloride+Tropicamide+1% Pilocarpine	憲齋觸觸築鑰夢鏇獵夢 = 襯衊願願淵糧繭網遞鹽築鏇鏇網襯簾獵淵襯顧 (範齋簾積壓顧鹹繭齋願, 觸窪鹽膚觸壓鹹觸構範 ~ 築鬱製淵夢鬱選築膚餘) 更多	-	2023-03-07
NCT03885011 (CTgov)	临床2期	老花眼	166	pilocarpine HCl+diclofenac Na (CSF-1-FDC)	構網糧鏇構鏇鏇鹽糧鑰 = 構選網憲網觸齋醖糧蓋醖構窪積簾襯選簾夢夢 (艱遞範築選獵選積繭鑰, 鬱蓋築簾壓獵餘齋鏇膚 ~ 憲築觸構簾鏇觸窪夢鹽) 更多	-	2023-01-26
				pilocarpine HCl (Pilo)	構網糧鏇構鏇鏇鹽糧鑰 = 鬱繭膚廠廠廠選範獵襯醖構窪積簾襯選簾夢夢 (艱遞範築選獵選積繭鑰, 醖顧鬱壓網襯淵淵壓淵 ~ 製齋遞醖衊繭簾鏇獵齋) 更多